This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The longterm goal of this study is to understand the role of viral immune modulators for monkeypox virus (MPV) and cowpox virus (CPV) virulence. Individuals infected with MPV during the 2003 outbreak developed a strong MPV-specific T cell response, but the MPV-specific T cells were not stimulated by MPV-infected antigen presenting cells (APC) in vitro . In contrast, infection of APC by the vaccine strain Vaccinia-virus (VV) WR activated cross-reactive CD8+ and CD4+ T cells from MPV-infected individuals. These data strongly suggest that MPV prevents T cell stimulation by expressing immunomodulators that are absent in VV. Similarly, we observed that CPV-infected cells did not stimulate T cells. We succeeded in identifying the gene products of CPV that are responsible for T cell evasion. The results were recently published . We are currently evaluating homologous genes in the MPV-genome for their ability to inhibit T cell stimulation.